Abstract
Tumor Necrosis Factor-alpha (TNF-α) was reported to increase autophagy in rheumatoid arthritis human fibroblast-like synovial cell (RA-HFLS). We investigated different levels of TNF-α exposed to RA-HFLS by focusing on the relationship of autophagy and apoptosis. RA-HFLS and normal human fibroblast-like synovial cell (HFLS) were stimulated by TNF-α in the presence or the absence of 3-methyladenine (3-MA) or chloroquine (CQ). Cell apoptosis was detected by flow cytometry. Autophagy was determined through the expression levels of LC3, Beclin1, and P62 measured by Western Blot analysis as well as Confocal Laser Scanning Microscopy. The basal autophagy level was significantly higher in RA-HFLS than in HFLS. Autophagy was enhanced both in RA-HFLS and HFLS when they were treated with TNF-α. With the treatment of TNF-α, a slightly higher autophagy level was found in RA-HFLS than in HFLS, without a dose dependent effect. When autophagy was inhibited by 3-MA or CQ, apoptosis increased in both groups. With the stimulation of different doses TNF-α, apoptosis was much higher in HFLS group than in RA-HFLS. Autophagy is a protection mechanism when treated by TNF-α in RA-HFLS.
Highlights
Rheumatoid arthritis (RA) is the most common autoimmune disease characterized by chronic inflammation and joint destruction [1, 2]
It is widely accepted that this inflammatory cell infiltration and destructive features in joint are driven by resident rheumatoid arthritis human fibroblast-like synovial cell (RA-human fibroblastlike synovial cell (HFLS))
When RA-HFLS and HFLS were treated with TNF-α at concentration of 30ng/ml for 48h, autophagy was increased both in RA-HFLS group and HFLS group (3.2 fold, 3.0 fold), and HFLS group has a large range of increment compared to the RA-HFLS group
Summary
Rheumatoid arthritis (RA) is the most common autoimmune disease characterized by chronic inflammation and joint destruction [1, 2]. It is widely accepted that this inflammatory cell infiltration and destructive features in joint are driven by resident rheumatoid arthritis human fibroblast-like synovial cell (RA-HFLS). Some evidence indicates that RA-HFLS appears to change its phenotype like tumor cells, which show invasive hyperplastic and lacking apoptosis [5]. Accumulating evidence indicates that autophagy appears to have a dual role in eukaryotic cells. It manifests cytoprotective effects through offering nutrient and the clearance of unnecessary materials and pathogens. Large amounts of evidence indicate that autophagy protects various cells from apoptosis [8, 9]. Compared with normal human fibroblastlike synovial cell (HFLS), increased induction of autophagy may be associated with resistance-apoptosis in RA-HFLS [10, 11]
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